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Lipid management with diet or dietary supplements

Lipid management with diet or dietary supplements
Authors:
Christine C Tangney, PhD
Robert S Rosenson, MD
Section Editors:
Mason W Freeman, MD
David Seres, MD
Deputy Editor:
Jane Givens, MD, MSCE
Literature review current through: Nov 2022. | This topic last updated: Apr 14, 2022.

INTRODUCTION — Improvement in serum lipids can be achieved through lifestyle changes including dietary modification [1,2]. A dietary approach to lipid management, including an overall change in dietary pattern, the use of specific dietary components, and the use of supplements, may be used with or without adjunctive pharmacotherapy to achieve lipid goals.

The efficacy of dietary modifications and supplements in improving serum lipids will be reviewed here. The indications and rationale for lipid lowering in the primary and secondary prevention of cardiovascular disease and the specific management of severe hypertriglyceridemia is reviewed elsewhere. Furthermore, only the effects of dietary modifications on lipids will be reviewed here; the cardiovascular and other health outcomes of these dietary interventions are reviewed elsewhere.

(See "Low-density lipoprotein cholesterol-lowering therapy in the primary prevention of cardiovascular disease".)

(See "Management of low density lipoprotein cholesterol (LDL-C) in the secondary prevention of cardiovascular disease".)

(See "Hypertriglyceridemia in adults: Management".)

(See "Healthy diet in adults", section on 'Specific healthy dietary patterns'.)

OUR APPROACH

Dietary modification for all individuals — For all individuals in whom lipid management is indicated, we suggest dietary modification as part of initial therapy. Additional lifestyle modifications, including weight loss and exercise, are also components of the initial comprehensive approach to lipid management. (See "Overview of primary prevention of cardiovascular disease", section on 'Major components' and "Low-density lipoprotein cholesterol-lowering therapy in the primary prevention of cardiovascular disease".)

Our approach to dietary modification for lipid management is as follows:

For patients with dyslipidemia, whether or not they are on concurrent lipid-lowering pharmacologic therapy, we encourage adherence with one of the following general dietary patterns known to improve serum lipids:

Mediterranean diet

Dietary Approaches to Stop Hypertension (DASH) diet

Vegetarian (or other meat restricted) diet

Low-carbohydrate diet

Avoidance of trans fats

Such dietary changes, particularly in patients with poor baseline diets, can improve low-density lipoprotein (LDL) cholesterol by as much as 17 to 29 percent [3,4]. Many of the dietary patterns that can improve lipids have additional health benefits, including a reduction in the risk of cardiovascular disease and reduced blood pressure and weight. (See "Obesity in adults: Dietary therapy", section on 'Low-fat diets' and "Obesity in adults: Dietary therapy", section on 'Low-carbohydrate diets' and "Healthy diet in adults", section on 'DASH diet' and "Healthy diet in adults", section on 'Mediterranean diet'.)

For individuals who are unwilling or unable to make sweeping changes to their overall dietary pattern, we encourage the inclusion of specific dietary components known to improve lipids. These constituents should ideally be substituted for another dietary component known to be associated with detrimental effects on lipids or other metabolic parameters. As examples:

Substituting soy-based products (such as tofu or tempeh) for any meat in recipes

Substituting a lean meat such as (non-fried) poultry or fish (other than shrimp) for red meat in recipes

Replacing refined grain products with higher-fiber whole-grain products whenever possible

Drinking tea, carbonated water, or plain water instead of sugar-sweetened soft drinks and fruit juices

Using a nut butter spread instead of traditional dairy butter

In addition to using these components as substitutes for other foods, nuts, high-fiber foods, and fiber supplements may also be added to any diet to improve lipids.

There are several dietary supplements that have beneficial effects on lipids, including omega-3 fatty acids, red yeast rice, berberine, and green tea extracts. While these may be considered for use as adjunctive therapy for lipid management, they are a complement to the dietary approach, and not a pillar of treatment.

Prior to recommending a diet or a specific dietary pattern, we evaluate an individual's comorbidities, dietary preferences, and lipid-lowering requirements. In particular, we consider the specific circulating lipid fractions that are elevated (eg, LDL cholesterol and/or triglycerides) or reduced (eg, high-density lipoprotein [HDL] cholesterol). As examples:

For individuals with elevated LDL cholesterol, we advise a reduction in saturated fat and total caloric intake.

For those with isolated hypertriglyceridemia, we advise a low-carbohydrate diet with a reduced total caloric intake.

For patients who are overweight, with elevated triglycerides and/or low HDL cholesterol, and for patients with pre-diabetes and fatty liver disease, we typically advise following a Mediterranean diet.

Furthermore, individuals with specific comorbidities (eg, diabetes mellitus and hypertension) may need to restrict certain macronutrients and/or minerals (eg, high glycemic load carbohydrates and sodium); those with allergies may need to avoid certain foods; and some people may need to follow a meat-restricted diet due to personal preference or religious reasons. In addition, consideration should be given to a patient's medication regimen before initiation of any dietary change (eg, possible need to alter a hypoglycemic regimen in a patient with diabetes mellitus after initiation of a low-carbohydrate diet). No single diet is appropriate for all people.

Mediterranean diet – There is no single Mediterranean diet, but such diets are typically high in fruits, vegetables, whole grains, beans, nuts, and seeds and include olive oil as an important source of fat; there are typically low to moderate amounts of fish, poultry, and dairy products, and there is little red meat. (See "Healthy diet in adults", section on 'Mediterranean diet'.)

Following a Mediterranean diet may lead to a reduction in total cholesterol. For example, in a 2011 meta-analysis of six randomized trials comparing a Mediterranean with a low-fat diet in 2650 individuals with overweight or obesity, a Mediterranean diet led to a greater reduction in total cholesterol (-7.4 mg/dL, 95% CI -10.3 to -4.4) but a nonsignificant reduction in LDL cholesterol (-3.3 mg/dL, 95% CI -7.3 to +0.6 mg/dL [5]. A Mediterranean diet may also decrease LDL oxidation [6].

Following a Mediterranean diet can also improve triglyceride levels, particularly in individuals with type 2 diabetes mellitus [7,8].

While a Mediterranean diet appears to reduce the risk of cardiovascular events, it is uncertain whether the cardiovascular benefits of a Mediterranean diet are due to its lipid effects. (See "Healthy diet in adults", section on 'Mediterranean diet'.)

DASH diet – The DASH diet is rich in fruits and vegetables, high in fiber, moderate in low- or non-fat dairy products, low in animal protein, and low in saturated fat and contains many plant sources of protein including legumes and nuts [9,10]. (See "Diet in the treatment and prevention of hypertension", section on 'Dietary Approaches to Stop Hypertension trial' and "Healthy diet in adults", section on 'DASH diet'.)

Adhering to a DASH diet may improve serum lipid profile, although the results may vary with medical comorbidity. In a trial of 430 healthy adults, following the DASH diet for eight weeks decreased total cholesterol, LDL cholesterol, and HDL cholesterol compared with a control diet [10]. However, in trial of 80 adults with type 2 diabetes mellitus, following the DASH diet decreased LDL cholesterol and increased HDL cholesterol compared with a control diet [11]. Triglycerides were unchanged in both trials.

Modification of the DASH diet results in further improvements in serum lipids. For example, in the OmniHeart trial, the carbohydrate content of the DASH diet was reduced (from 58 to 48 percent of energy) and partially replaced with either protein or unsaturated fat [12,13]. Compared with the traditional DASH diet, the protein-replaced diet (25 versus 15 percent of energy) further decreased LDL cholesterol (by 3.3 mg/dL), HDL cholesterol (by 1.3 mg/dL), and triglycerides (by 15.7 mg/dL); the unsaturated fat-replaced diet (31 versus 21 percent of energy) had no effect on LDL cholesterol but lowered triglycerides (by 9.6 mg/dL) and increased HDL cholesterol (by 1.1 mg/dL).

One of the critical components of the DASH diet pattern is the restriction of saturated fat, which can be achieved through a reduction in the frequency of consumption of red and processed meats, as well as pork, lamb, and the highly saturated coconut, palm, and palm kernel oils. In a meta-analyses of 36 randomized controlled trials, a reduction in dietary intake of red meat alone did not lower LDL cholesterol, but a reduction of red meat intake combined with dietary replacement with high-quality plant-based protein (eg, soy, nuts, legumes) improved total and LDL cholesterol [14].

Vegetarian (and similar meat-restricted) diets – In addition to a vegetarian diet pattern (a diet that excludes only animal flesh), there are many other variations of meat-restricted diets (eg, vegan, ovovegetarian, lactovegetarian, lacto-ovovegetarian) that may improve serum lipid profiles. As an example, in a meta-analysis of 11 trials comparing meat-restricted with omnivorous diets, following a vegetarian diet lowered total cholesterol (-13.9 mg/dL, 95% CI -21.3 to -6.6 mg/dL), LDL cholesterol (-13.1 mg/dL, 95% CI -22.0 to -4.2 mg/dl, and HDL cholesterol (-3.9 mg/dL; 95% CI -5.4 to -2.3 mg/dL) [15]. There was no reduction in serum triglycerides.

A modified vegetarian diet pattern that includes the addition of four cholesterol-lowering foods (plant stanols, soluble fiber, nuts, and soy protein) may have a larger effect among individuals with hyperlipidemia [3,16]. In a meta-analysis of seven randomized trials, for example, those following this diet for four weeks had a lower LDL cholesterol (-28 mg/dL, 95% CI -34.4 to -21.7 mg/dL) and triglycerides (-24.8 mg/dL 95%, CI -37.3 to -12.4 mg/dL) compared with those following a National Cholesterol Education Project (NCEP) Step II diet (<7 percent of total energy as saturated fats and cholesterol intake of <200 mg/day) [4]. There was no reduction in serum HDL cholesterol.

Low-carbohydrate diet – Low-carbohydrate diets vary in the quantity and types of carbohydrate they contain, but in general, such a diet is limited to less than 130 g/day of carbohydrates (with less than 60 g/day considered a very low carbohydrate diet). (See "Obesity in adults: Dietary therapy", section on 'Low-carbohydrate diets'.)

A low-carbohydrate diet may have a beneficial effect on serum lipids, although the effects may be in part due to weight loss. In a randomized trial comparing three dietary patterns (low-fat, Mediterranean, and low-carbohydrate diets) in over 300 adults with overweight and obesity, weight loss and increased HDL cholesterol occurred in all groups at 24 months, with the largest weight loss and HDL cholesterol increase seen among those on the low-carbohydrate diet (-5.5 kg and 8.4 mg/dL, respectively) [17]. Those on the Mediterranean and low-carbohydrate diets had the largest reduction in triglycerides (-21.8 and -23.7 mg/dL, respectively).

Diet low in trans fatty acids – Trans fatty acids (trans fats) are a type of unsaturated fat produced as a result of the industrial hydrogenation of naturally occurring polyunsaturated fats [18]. Although some trans fats occur naturally in foods of animal origin, the majority of dietary trans fats come from prepared foods, such as cakes, cookies, commercially prepared fried foods, and some margarines. Replacement of dietary trans fatty acids with cis-polyunsaturated fatty acids lowers total cholesterol, LDL cholesterol, triglycerides, and apolipoprotein B (apo B) and raises HDL cholesterol [19,20]. (See "Dietary fat", section on 'Trans fatty acids'.)

While comprehensive changes to diet composition are the preferred dietary strategy for lipid management, there are specific foods and dietary components which may improve serum lipids when added to a "regular" diet. Before incorporating any of these foods into the diet, each patient's unique medical needs and preferences should be considered.

Dietary fiber – The consumption of certain soluble fibers, including psyllium, pectin, wheat dextrin, certain beans (eg, navy, pinto, and black beans), lentils, nuts, and oat products, can produce a reduction in both total cholesterol and LDL cholesterol. Fiber is effective whether added to the diet as a supplement or used as a component of a dietary modification plan (eg, substituting whole grains for processed carbohydrates).

The primary mechanism of action differs according to fiber type but may include slower gastric emptying, enhanced satiety, inhibition of hepatic cholesterol synthesis, and/or enhanced fecal excretion of cholesterol and bile salts [21]. In addition, the molecular weight and amount of beta-glucan in food products such as oats may contribute to LDL cholesterol lowering [22]. The gel-forming attributes of soluble fiber may be the basis for improved lipid profiles and glucose homeostasis [23,24].

Representative studies of the beneficial effects of fiber include:

In one meta-analysis, there was a reduction in both total cholesterol and LDL cholesterol with increased consumption of soluble fiber [21]. For every gram increase in dietary soluble fiber, the LDL cholesterol decreased by an average of 2.2 mg/dL. Total cholesterol levels decreased by fiber type: oat-based fibers (-0 to -18 percent); psyllium (-3 to -17 percent); pectin (-5 to -16 percent); and guar gum (-4 to -17 percent). Triglycerides and HDL cholesterol were unchanged.

In a meta-analysis of randomized trials of patients with both normal and elevated cholesterol levels, the addition of 10.2 g/day of psyllium lowered the LDL cholesterol by an average of 12.8 mg/dL [25].

Among patients receiving simvastatin 10 mg/day, the addition of 15 g/day of psyllium (5 g three times daily with meals) resulted in a reduction in LDL cholesterol levels equivalent to that seen in those taking simvastatin 20 mg/day [26].

In a meta-analysis of randomized trials, whole-grain diets reduced LDL cholesterol and total cholesterol, with whole-grain oats having the greatest effect on total cholesterol levels (average reduction of 6.6 mg/dL) [27]. Triglycerides and HDL cholesterol were not changed.

A high-fiber diet may not be appropriate for all individuals, such as those with chronic bowel strictures from inflammatory bowel disease or those requiring bowel "rest" due to acute bowel inflammation (eg, from acute diverticulitis or flare of inflammatory bowel disease).

Nuts – The consumption of nuts that are high in mono- or polyunsaturated fatty acids (particularly walnuts, almonds, pistachios, macadamia nuts, pecans, and hazelnuts) may improve serum cholesterol. As examples:

In randomized trials, walnuts, which are rich in polyunsaturated fatty acids, especially omega-3 fatty acids, had a beneficial effect on serum lipids [28-30]. In one trial comparing a Mediterranean diet with a similar diet in which walnuts replaced 35 percent of the energy from monounsaturated fats, those on the walnut-replaced diet experienced a reduction in both total cholesterol (-10.8 mg/dL, 95% CI -16.8 to -4.8 mg/dL) and LDL cholesterol (-11.2 mg/dL, 95% CI -16.3 to -6.1 mg/dL) [28]. In a second trial, a NCEP Step I diet was compared with a similar diet in which walnuts accounted for 20 percent of calories [29]. Those on the walnut-rich diet had a reduction in total cholesterol (-22.4 mg/dL, 95% CI -28 to -17 mg/dL), LDL cholesterol (-18.2 mg/dL, 95% CI -23.2 to -13.2 mg/dL), and HDL cholesterol (-2.3 mg/dL, -3.9 to -0.7 mg/dL) but no change in triglycerides.

Improvement in serum cholesterol was also seen with the consumption of almonds, which are high in monounsaturated fats and fiber [31,32]. In a trial including 30 overweight or obese adults, daily consumption of almonds (42 g/day) reduced total cholesterol and LDL cholesterol (by 4 and 7 percent respectively) [31]. There was no change in HDL cholesterol or triglycerides.

In addition to walnuts and almonds, similar lipid-lowering effects are seen with the consumption of other nuts including pistachios, hazelnuts, pecans, macadamia nuts, and pistachios [33,34]. As an example, in the PREDIMED trial, a Mediterranean diet supplemented with nuts (30 g of nuts, including 15 g walnuts, 7.5 g hazelnuts, and 7.5 g almonds) lowered total cholesterol, LDL cholesterol, and triglycerides compared with a control diet [35]. In addition, in a meta-analysis including 61 trials evaluating the lipid-lowering effects of tree nuts, there was a greater reduction in lipids (total cholesterol, LDL cholesterol, apo B, and triglycerides) with increased nut intake; the dose response to nut intake was nonlinear, with stronger effects at higher nut doses [36].

Nuts also contain significant amounts of fiber, and a diet rich in nuts may not be appropriate for individuals requiring a low-fiber diet (eg, those with chronic bowel strictures or acute bowel inflammation). In addition, consumption of nuts is contraindicated among those with nut allergies.

Soy – Soy is an excellent source of protein and also contains isoflavones, which are phytoestrogens. Isoflavones have some properties similar to estrogen and may have a small effect on cholesterol levels and inhibition on LDL oxidation [37]. The efficacy of soy on improving serum lipids is modest; although soy and soy based products may be added to a diet, we agree with the conclusions of the American Heart Association [38,39]:

Although the effect of soy consumption alone is modest, it may produce a meaningful reduction on total cholesterol and LDL cholesterol when combined in the diet with other cholesterol-lowering foods [39].

When substituted for animal-derived foods, many soy foods and food products (eg, tofu, soy butter, edamame, some soy burgers, etc) are likely to have beneficial effects on lipids and cardiovascular health because they are low in saturated fats, high in unsaturated fats, and often rich in fiber [38].

Isoflavone supplements do not appear to be of benefit and should not be taken with a goal of improving lipids and cardiovascular risk [38]. (See 'Supplements that we do not recommend' below.)

Although earlier trials and a meta-analyses had suggested important lipid benefits with consumption of soy protein [40-42], a subsequent systematic review concluded that the benefits of soy consumption were small and that isoflavones alone had no beneficial effect [38]. When large amounts of soy protein (average 50 g/day) were substituted for other dietary proteins, LDL cholesterol concentrations decreased by an average of 3 percent; there was no effect on HDL cholesterol, triglycerides or apolipoprotein a (apo A). In addition, soy isoflavones alone had no effect on LDL cholesterol or other lipids. In a 2019 meta-analysis of 46 randomized trials of soy consumption, the modest benefits of soy intake on total cholesterol and LDL cholesterol levels were confirmed [39].

Consumption of soy products may also have some adverse lipid effects. As an example, in a trial including 200 healthy men and postmenopausal women, soy improved both blood pressure and lipids but increased serum lipoprotein a levels (in men only) [43].

In addition, there is concern regarding the role of excessive phytoestrogen intake in women due to its pro-estrogen effects. Although there is no convincing evidence that soy intake affects the incidence of estrogen-dependent cancers (ie, breast and endometrial), based upon the theoretical risk of stimulating estrogen receptors with phytoestrogens, some experts suggest that women with a personal history of breast cancer moderate their soy intake to minimize this risk. (See "Factors that modify breast cancer risk in women", section on 'Other dietary factors' and "Approach to the patient following treatment for breast cancer", section on 'Physical activity, diet, and body weight'.)

Plant sterols and stanols – Plants contain a number of sterols, stanols, and their esters that can lower serum cholesterol; these compounds are similar in chemical structure to cholesterol, differing in their side chain configuration. Plant sterols differ from plant stanols in that the B ring contains an unsaturated bond.

The mechanism by which sterols and stanols lower cholesterol involves inhibition of cholesterol absorption [44,45], mostly through disruption in intraluminal solubilization [46]. The decrease in serum cholesterol is less than that expected by the degree of reduced absorption, however, likely due to a compensatory increase in hepatic cholesterol synthesis [47].

There are naturally occurring sterols and stanols in nuts, legumes, whole grains, fruits, vegetables, and plant oils. In addition, a number of manufactured products enriched with plant sterols and stanols are commercially available. The margarines containing these compounds (eg, Benecol and Take Control spreads) have been available the longest and are the most studied [48]. Sitostanol and campestanol are the main sterols present in Benecol spread; Take Control spread contains sitosterol and campesterol.

Foods enriched with plant sterols and/or stanols may be used as an adjunct to dietary modification and pharmacotherapy in patients with elevated LDL cholesterol, although long-term safety information and evidence on reduction in cardiovascular outcomes is lacking. An advisory from the Nutrition Committee of the American Heart Association concluded that although foods enriched with plant sterols and/or stanol esters are a promising addition to dietary intervention aimed at improving cardiac risk profiles [18], there is little evidence for their safety beyond two years [49]. In addition, among patients with sitosterolemia (a rare, autosomal recessive disease characterized by hyperabsorption of dietary sterols, stanols, and cholesterol), increased consumption of plant sterols and stanols may lead to adverse health consequences, including an increased risk of atherosclerotic vascular disease. (See "Familial hypercholesterolemia in adults: Overview", section on 'Differential diagnosis'.)

Several studies have examined the efficacy of plant stanol and sterol-enriched margarines for lowering cholesterol:

In a trial of 150 patients with mild hypercholesterolemia, people were randomly assigned to consume sitostanol fortified margarine or unfortified margarine [47]. Those consuming the fortified margarine experienced a 10 to 14 percent decrease in total cholesterol and LDL cholesterol; the decrease occurred predominantly in the first three months, although values continued to decline over the subsequent 12 months of treatment. There were no differences in HDL cholesterol and triglycerides between the groups.

In a trial including 22 postmenopausal women with coronary heart disease, consumption of sitostanol fortified margarine lowered total cholesterol and LDL cholesterol compared with consumption of unfortified margarine (13 versus 5 percent; 20 versus 5 percent) [50].

Stanol-enriched margarine can further reduce serum cholesterol in patients already taking a statin drug. As examples:

In one trial of patients with LDL cholesterol ≥130 mg/dL despite at least three months of statin therapy, the addition of 5.1 g/day of plant stanol ester for eight weeks reduced total cholesterol (by 12 versus 5 percent) and LDL cholesterol (by 17 versus 7 percent) compared with placebo [51].

In a trial of 10 women with coronary artery disease taking simvastatin, consumption of sitostanol fortified margarine for 12 weeks reduced total cholesterol and LDL cholesterol compared with simvastatin alone (by 11 and 16 percent respectively) [50].

The frequency and timing of sterol and/or stanol intake as well as the food delivery vehicle also impacts the efficacy of LDL cholesterol lowering. Once-daily intake is less effective than more frequent intake, and consumption with rather than between meals also optimizes efficacy [52-54]. In addition, in two meta-analyses, greater cholesterol-lowering benefit was seen from sterol-enriched spreads and margarines than from milk and juices [55,56].

Responses to plant sterol ester-containing spreads may vary by apolipoprotein E (apo E) genotype [57].

Plant sterols and stanols may also lower triglycerides. As an example, in normotriglyceridemic adults, dietary supplementation with these compounds (from 1.6 to 9 g/day) for one to two months reduced triglycerides from 0.8 to 7 percent [55,58]. Furthermore, in trials including individuals with elevated serum triglycerides (>150 mg/dL), sterol and/or sterol supplementation (1.8 to 4 g/day) reduced serum triglycerides by 11 to 28 percent [59,60].

Polyphenols – Polyphenols, substances with antioxidant effects, are found primarily in plants (and in plant-based foods) such as tea (see 'Supplements that we do not recommend' below), coffee, cocoa, olive oil, and red wine [61,62]. They include flavonoids and flavonoid derivatives, lignans, phenolic acids, and stilbenes [63]. There is some evidence that consumption of polyphenols in foods has favorable effects on serum lipids.

As an example, in a trial of 200 healthy men, the effects of virgin olive oil (high in polyphenols), refined olive oil (low in polyphenols), and a mixture of the two (with intermediate polyphenol content) on serum lipids were compared [64]. Dose-response effects on both LDL cholesterol and HDL cholesterol were seen, with high-polyphenol olive oil raising HDL cholesterol and lowering LDL cholesterol more than low-polyphenol olive oil.

Resveratrol, a stilbene that occurs naturally in several plants, including red grape skin, blueberries, peanuts, and cocoa, has been attributed various health benefits due to antiinflammatory and antiatherogenic properties. Foods rich in resveratrol may have beneficial lipid effects. As an example, in a trial of adults with metabolic syndrome, consumption of one cup of blueberries daily for six months increased HDL cholesterol (3.1 mg/dL), HDL particle density, and apo A-1 [65].

Dietary supplements that may be of benefit — There are several dietary supplements that may have a beneficial role in lipid management, including omega-3 fatty acids, red yeast rice, and polyphenols. These supplements would ideally be used in conjunction with a dietary pattern known to improve lipids but may be added to a "regular" diet.

Omega-3 fatty acids – Consumption of omega-3 fatty acids can reduce triglycerides but may also affect (raise or lower) cholesterol levels. In particular, omega-3 fatty acids may increase total cholesterol and LDL cholesterol, particularly among those with elevated triglycerides [66,67]. Dose, source (food versus supplement), and composition of the omega-3 fatty acid (eicosapentaenoic acid [EPA] alone or EPA plus docosahexaenoic acids [DHA]) can markedly modify lipid responses. Rich food sources of omega-3 fatty acids include fatty fish (especially salmon, herring, mackerel, and trout) and fish oil and plant products such as flaxseed, chia seeds, canola oil, soybean oil, and some nuts. (See "Dietary fat", section on 'Polyunsaturated fatty acids' and "Fish oil: Physiologic effects and administration", section on 'System effects' and "Hypertriglyceridemia in adults: Management", section on 'Marine omega-3 fatty acids'.)

There is high-quality evidence supporting the reduction in triglycerides from many omega-3 fatty acid-containing products [56,68-70]. As an example:

In a meta-analysis of 55 trials, each 1 g/day increase in EPA+DHA reduced triglycerides by 5.9 mg/dL [71]. The effect was stronger when baseline triglyceride levels were higher; above the median triglyceride level of 83 mg/dL, each 1 g/day EPA+DHA reduced triglycerides by 8.4 mg/dL.

In addition, omega-3 fatty acids may also affect LDL and HDL cholesterol levels, although the results are mixed and dependent upon the source and composition of the omega-3 fatty acid consumed. As examples:

In a meta-analysis including seven trials and 662 participants, krill oil supplementation (1 to 4 g/day for 24 weeks) reduced LDL cholesterol (-15.5 mg/dL, 95% CI -28.4 to -2.6 mg/dL) and triglycerides (-14.0 mg/dL, 95% CI -21.4 to -6.7 mg/dL) [72]. In addition, plasma concentrations of HDL cholesterol were increased (6.6 mg/dL, 95% CI 2.3 to 11.0 mg/dL).

In a meta-analyses including 28 trials, the consumption of flaxseeds (whole, ground, or defatted, 20 to 50 g/day) reduced total cholesterol (-7.3 mg/dL; 95% CI -11.2 to -3.5 mg/dL) and LDL cholesterol (-6.2 mg/dL; 95% CI -9.7 to -2.3 md/dL); there was no effect on triglycerides or HDL cholesterol [73]. However, the consumption of flaxseed oil had no effect on serum lipids [73].

In some patients, however, DHA modestly raises low-density LDL cholesterol (by 3 to 5 percent), which may be due to an increase in the proportion of large "fluffy" LDL cholesterol particles and reductions in small, dense LDL cholesterol particles [74-76]. The clinical significance of this modest LDL cholesterol increase and change in particle size in relation to the change in total LDL particle concentration is unclear [77]. While an increase in overall LDL particle size has been reported with omega-3 fatty acids [78-80], not all trials support these results [81].

Since many omega-3 preparations lower plasma triglyceride concentrations, which is a determinant of small dense LDL particles, it is also possible that these can decrease the concentration of small LDL particles. Support for this hypothesis comes from the observed reduction of cholesteryl ester transfer activity following fish oil therapy [82].

Red yeast rice – Red yeast rice is a fermented rice product, most often taken as a supplement, which can improve serum cholesterol [83]. It contains varying amounts of a family of naturally occurring substances called monacolins that have HMG CoA reductase inhibitor (statin) activity [84]. (See "Statins: Actions, side effects, and administration".)

In addition, other active ingredients in red yeast rice that may affect cholesterol lowering include sterols (beta-sitosterol, campesterol, stigmasterol, sapogenin), isoflavones, and monounsaturated fatty acids [85].

Although red yeast rice is effective in lipid lowering, due to the variability in potency and possible adulteration of commercially available products, we strongly prefer that our patients take a prescription statin medication rather than these supplements.

Representative studies of the efficacy of red yeast rice in lowering total cholesterol and LDL cholesterol include [85-87]:

In a trial including 83 patients with hyperlipidemia, red yeast rice supplements (2.4 g/day) or placebo were given for eight weeks; all trial participants followed a cholesterol-lowering diet (American Heart Association Step 1 diet) [85]. Red yeast rice supplements lowered total cholesterol (208 versus 251 mg/dL) and LDL cholesterol (135 versus 175 mg/dL) compared with placebo. HDL cholesterol levels were unchanged.

One of the monacolins in the red yeast rice extract used in this study, monacolin K, is the active ingredient in the HMG CoA reductase inhibitor lovastatin. The daily monacolin K content of red yeast rice was 0.2 percent of the total product, which at a total dose of red yeast rice of 2.4 g/day translates into an equivalent daily lovastatin dose of 4.8 mg. This is lower than the average 20 to 40 mg dose of lovastatin typically used, suggesting that other active ingredients in red yeast rice probably also contribute to its cholesterol-lowering activity [84].

In a trial including patients with dyslipidemia who had previously discontinued statin therapy due to myalgia, treatment with red yeast rice (1800 mg twice daily for 24 weeks) was compared with placebo; all patients participated in similar lifestyle modifications [87]. Red yeast rice supplementation was well tolerated while achieving greater reductions in both total cholesterol (-15 versus -5 percent) and LDL cholesterol (-21 versus -9 percent) compared with placebo. There was no change in HDL cholesterol.

Due to the lack of standardization, there is substantial variability across commercially available red yeast rice preparations [88-90]; this may affect individual clinical results. As an example, in a study that evaluated the content of 12 preparations of commercially available red yeast rice, the total monacolin content ranged from 0.31 to 11.15 mg/capsule, and the monacolin K (lovastatin) content ranged from 0.10 to 10.09 mg/capsule. Furthermore, four of the preparations had elevated levels of citrinin, a potentially nephrotoxic mycotoxin [89]. Finally, while short-term studies (up to four months) have found red yeast rice to be safe, no long-term studies have been performed [84]. (See "Overview of herbal medicine and dietary supplements", section on 'Standardization' and "Overview of herbal medicine and dietary supplements", section on 'Purity and Adulteration'.)

Berberine – Berberine is an alkaloid found in the root, fruit, or bark of a number of plants such as goldenseal, Oregon grape, barberry, and tree turmeric. It reduces serum cholesterol levels through several mechanisms, including reduction of intestinal cholesterol absorption, enhanced fecal cholesterol excretion [91,92], inhibition of proprotein convertase subtilisin kexin 9 (PCSK9) [93], and upregulation of LDL receptors [94]. In a meta-analysis including six trials and 229 patients with hyperlipidemia, the addition of berberine supplements (between 900 to 1500 mg/day) improved total cholesterol (-25.5 mg/dL; 95% CI -39.4 to -12 mg/dL), LDL cholesterol (-25.1 mg/dL; 95% CI -29 to -21.7 mg/dL), and triglycerides (-34.5 mg/dL; 95% CI -52.3 to -16.8) compared with placebo or lifestyle modification [95].

Probiotics – Probiotics, living microorganisms which are naturally present in fermented foods, may reduce serum cholesterol. Probiotics may also be added to food products and are available as dietary supplements. There are seven common genera of microorganisms used in probiotic products; these include Lactobacillus, Bifidobacterium, Saccharomyces, Streptococcus, Enterococcus, Escherichia, and Bacillus.

In a meta-analysis including 30 randomized controlled trials and over 1600 participants, treatment with probiotics for 3 to 12 weeks lowered total and LDL cholesterol concentrations compared with placebo (-7.8 mg/dL, 95% CI -10.4 to -5.2 mg/dL; and -7.3 mg/dL, 95% CI -10.1 to -4.4 mg/dL, respectively) [96]. Lactobacillus acidophilus, a mixture of Lactobacillus acidophilus and Bifidobacterium lactis, and Lactobacillus plantarum were associated with significant reductions in total and LDL cholesterol, while Lactobacillus helveticus and Enterococcus faecium were not.

In another meta-analysis including 11 randomized controlled trials and 602 participants with normal or elevated cholesterol levels, treatment with probiotics for 2 to 10 weeks also reduced total and LDL cholesterol levels compared with placebo (-6.6 mg/dL, 95% CI -10.44 to -2.71 mg/dL; and -8.51 mg/dL, 95% CI -11.6 to -5.03 mg/dL, respectively) [97].

Additional studies suggest that probiotics added to dairy formulations may be beneficial in lowering total and LDL cholesterol compared with probiotics alone (in capsule form) [98].

Additional research on the efficacy of probiotics for lipid management is warranted.

SUPPLEMENTS THAT WE DO NOT RECOMMEND — A variety of products including plant-based based extracts and mineral supplements have been promoted for their overall health benefits and lipid-lowering effects. However, based upon the available evidence, we do not support the use of the following products for lipid management:

Tea and tea catechins – Consumption of tea, tea extracts, and green tea catechin supplements may have a beneficial effect on lipids, although they are not recommended for use in lipid management. In a 2013 meta-analysis of 11 randomized trials, consumption of green or black tea reduced low-density lipoprotein (LDL) cholesterol but had no effect on high-density lipoprotein (HDL) cholesterol [99]. Further, in a year-long randomized trial of more than 900 healthy postmenopausal women, green tea catechin supplements (1315 mg catechins/day) reduced total and LDL cholesterol, had no effect on HDL cholesterol, but increased triglycerides [100]. These findings are consistent with those of other trials and meta-analyses [101-103]. However, because of a number of reported cases of severe hepatotoxicity associated with use of green tea infusions or supplements, they are not recommended for use in lipid management [104].

Selenium – Selenium supplementation has no effect on serum lipids [105].

Calcium – Results of randomized controlled trials of calcium supplementation are mixed, but there appears to be no beneficial effect of calcium supplementation on serum lipids [106,107].

Garlic – Although earlier, smaller trials suggested a benefit of garlic supplementation [108-112], a subsequent larger trial failed to demonstrate improvement in lipids with use of any of three different garlic preparations (raw, powdered, or aged) [113].

Policosanol – Policosanol is a drug extracted from sugar cane wax that contains a number of aliphatic alcohols. While previous studied suggested a reduction in serum lipids with policosanol, in a randomized trial there was no improvement in any measurement of serum lipids [114].

Coconut oil – Dietary supplementation with coconut oil is not associated with improvements in serum lipids [115,116].

Coconut water – Little information is available about coconut water with respect to lipid lowering. In terms of dietary components, it contains no measurable saturated fat, 3.7 g carbohydrates, and 1.1 g fiber per 100 g [115].

Bergamot – Bergamot is the common name of the fruit Citrus bergamia Risso. Improvements in serum lipids have been reported in small, uncontrolled trials of patients with metabolic syndrome, nonalcoholic fatty liver disease [117] and in hyperlipidemic patients resistant to statin treatment [118]. However, high-quality data on the effects of bergamot are lacking.

Resveratrol – Although lipid lowering with resveratrol supplements has been described in experimental models and in cell culture studies, the evidence is less conclusive in randomized human trials. As an example, in a 2013 meta-analysis including seven randomized trials and almost 300 subjects, no lipid parameters were altered with resveratrol supplementation [119].

Soy isoflavones – Soy isoflavone supplements do not appear to be of benefit [38] and should not be taken with a goal of improving lipids.

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Lipid disorders in adults".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

Basics topics (see "Patient education: Diet and health (The Basics)" and "Patient education: Can foods or supplements lower cholesterol? (The Basics)")

Beyond the Basics topics (see "Patient education: Diet and health (Beyond the Basics)" and "Patient education: High cholesterol and lipids (Beyond the Basics)" and "Patient education: High-fiber diet (Beyond the Basics)" and "Patient education: High cholesterol and lipid treatment options (Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS

Dietary modification with change in overall dietary pattern – For all individuals in whom lipid management is indicated, we recommend dietary modification as part of initial therapy rather than making no dietary changes (Grade 1B). Many of the dietary patterns that can improve lipids have additional health benefits, including a reduction in the risk of cardiovascular disease and reduced blood pressure and weight. Additional lifestyle modifications, including weight loss and exercise, are also components of the initial comprehensive approach to lipid management. (See 'Our approach' above.)

For patients with dyslipidemia, whether or not they are on concurrent lipid-lowering pharmacologic therapy, we encourage adherence with one of the following general dietary patterns known to improve serum lipids:

Mediterranean diet

Dietary Approaches to Stop Hypertension (DASH) diet

Vegetarian (or other meat restricted) diet

Low-carbohydrate diet

Avoidance of trans fats

Inclusion of specific dietary components can also improve lipids – For individuals who are unwilling or unable to make sweeping changes to their overall dietary pattern, we encourage the inclusion of specific dietary components (eg, soy, fiber, nuts) as substitutes for other dietary components known to be associated with detrimental effects on lipids. Nuts, high-fiber foods and fiber supplements, and foods rich in polyphenols may also be added to any diet to improve lipids. In addition, foods enriched with plant sterols and/or stanols may be used as an adjunct to dietary modification and pharmacotherapy in patients with elevated low-density lipoprotein (LDL) cholesterol, although long-term safety information and evidence on reduction in cardiovascular outcomes is lacking. (See 'Dietary modification for all individuals' above.)

Specific patient factors should be considered – Prior to recommending a diet or a specific dietary pattern, we evaluate an individual's comorbidities, dietary preferences, and lipid-lowering requirements. In particular, we consider the specific circulating lipid fractions that are elevated (eg, LDL cholesterol and/or triglycerides) or reduced (eg, high-density lipoprotein [HDL] cholesterol). (See 'Dietary modification for all individuals' above.)

Certain dietary supplements may be used as adjuncts to dietary modification – There are several dietary supplements that have beneficial effects on lipids, including omega-3 fatty acids, red yeast rice, berberine, and certain probiotics. While these may be considered for use as adjunctive therapy for lipid management, they are a complement to the dietary approach and not a pillar of treatment. (See 'Dietary supplements that may be of benefit' above.)

Many dietary supplements not recommended – We do not advise the use of tea or tea supplements, selenium, calcium, garlic, policosanol, coconut oil or water, bergamot, resveratrol, or soy isoflavone supplements for lipid management due safety concerns or a lack of high-quality evidence supporting their efficacy. (See 'Supplements that we do not recommend' above.)

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Topic 4561 Version 55.0

References